(MIL ri none)
Inotropic support in heart failure: Short-term IV therapy of acutely-decompensated heart failure
American College of Cardiology/American Heart Association heart failure (HF) guideline recommendations (ACCF/AHA [Yancy 2013]): To maintain systemic perfusion and preserve end-organ performance in patients with cardiogenic shock; bridge therapy in stage D HF unresponsive to guideline-directed medical therapy and device therapy in patients awaiting heart transplant or mechanical circulatory support; short-term management of hospitalized patients with severe systolic dysfunction presenting with low blood pressure and significantly depressed cardiac output; long-term management (palliative therapy) in select patients with stage D HF unresponsive to guideline-directed medical therapy and device therapy who are not candidates for heart transplant or mechanical circulatory support.
Hypersensitivity to milrinone or any component of the formulation
Inotropic support in heart failure: IV: Loading dose (optional, not recommended by ACCF/AHA 2013 heart failure guidelines; also see Note"): 50 mcg/kg administered over 10 minutes followed by a maintenance dose titrated according to hemodynamic and clinical response; Maintenance dose: IV infusion: 0.375 to 0.75 mcg/kg/minute; lower initial doses of 0.1 mcg/kg/minute (with final maintenance doses of 0.2 to 0.3 mcg/kg/minute) have also been recommended (HFSA [Lindenfeld 2010]). The ACCF/AHA 2013 heart failure guidelines recommend a maintenance dose of 0.125 to 0.75 mcg/kg/minute (ACCF/AHA [Yancy 2013]).
Note: When initiating an infusion of 0.5 mcg/kg/minute without a loading dose, significant hemodynamic changes seen at 30 minutes with similar effects on pulmonary capillary wedge pressure and cardiac index seen at 2 and 3 hours, respectively, compared to loading dose regimen (Baruch 2011).
Bridge to heart transplantation (off-label use): IV: 0.1 to 0.75 mcg/kg/minute; titrate to optimize clinical condition (Aranda 2003; Bhat 2006; Upadya 2004)
Postoperative inotropic support in heart transplant recipients (off-label use): IV: 0.375 to 0.75 mcg/kg/minute; use the lowest effective dose and wean as tolerated over the first 3 to 5 days (ISHLT [Costanzo 2010]).
Refer to adult dosing.
Cardiac output maintenance and postresuscitation stabilization (off-label use): IV, IO: Loading dose: 50 mcg/kg over 10 to 60 minutes followed by a maintenance infusion of 0.25 to 0.75 mcg/kg/minute (AHA 2010).
Manufacturer recommended adjustment:
CrCl 50 mL/minute/1.73 m2: Administer 0.43 mcg/kg/minute
CrCl 40 mL/minute/1.73 m2: Administer 0.38 mcg/kg/minute
CrCl 30 mL/minute/1.73 m2: Administer 0.33 mcg/kg/minute
CrCl 20 mL/minute/ 1.73 m2: Administer 0.28 mcg/kg/minute
CrCl 10 mL/minute/1.73 m2: Administer 0.23 mcg/kg/minute
CrCl 5 mL/minute/1.73 m2: Administer 0.2 mcg/kg/minute
Alternative Dosing Adjustments in Patients with Renal Impairment1CrCl (mL/min)
Starting dose (mcg/kg/min)
0.375
0.5
0.75
1Based on expert opinion
50
0.25
0.375
0.5
40
0.125
0.25
0.375
30
0.0625
0.125
0.25
20
Consider alternative therapy
0.0625
0.125
10
Consider alternative therapy
0.0625
5
Consider alternative therapy
Table has been converted to the following text.
Alternative Dosing Adjustments in Patients with Renal Impairment (based on expert opinion)
Starting dose: 0.375 mcg/kg/minute:
CrCl 50 mL/minute: 0.25 mcg/kg/minute
CrCl 40 mL/minute: 0.125 mcg/kg/minute
CrCl 30 mL/minute: 0.0625 mcg/kg/minute
CrCl ≤20 mL/minute: Consider alternative therapy
Starting dose: 0.5 mcg/kg/minute:
CrCl 50 mL/minute: 0.375 mcg/kg/minute
CrCl 40 mL/minute: 0.25 mcg/kg/minute
CrCl 30 mL/minute: 0.125 mcg/kg/minute
CrCl 20 mL/minute: 0.0625 mcg/kg/minute
CrCl ≤10 mL/minute: Consider alternative therapy
Starting dose: 0.75 mcg/kg/minute:
CrCl 50 mL/minute: 0.5 mcg/kg/minute
CrCl 40 mL/minute: 0.375 mcg/kg/minute
CrCl 30 mL/minute: 0.25 mcg/kg/minute
CrCl 20 mL/minute: 0.125 mcg/kg/minute
CrCl 10 mL/minute: 0.0625 mcg/kg/minute
CrCl 5 mL/minute: Consider alternative therapy
There are no dosage adjustments provided in the manufacturer 's labeling.
Loading dose (optional): May administer undiluted; diluting to a rounded total volume of 10 or 20 mL may simplify the visualization of the injection rate.
Maintenance dose: For a final concentration of 0.2 mg/mL: Dilute 1 mg/mL (20 mL) with 80 mL diluent (final volume: 100 mL) of 1/2NS, NS or D5W. May also dilute 1 mg/mL (10 mL) with 40 mL diluent (final volume: 50 mL).
For IV use only. Administer loading dose (optional) undiluted slowly over 10 minutes. Infuse maintenance dose via continuous infusion pump.
Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F); avoid freezing. Minimize exposure to heat; avoid excessive heat. Brief exposure up to 40 ‚ °C (104 ‚ °F) will not adversely affect drug. Stable at 0.2 mg/mL in 1/2NS, NS, or D5W for 72 hours at room temperature in normal light (Wilson 1986).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Generic: 200 mcg/mL (100 mL, 200 mL); 10 mg/10 mL (10 mL); 20 mg/20 mL (20 mL); 50 mg/50 mL (50 mL)
Solution, Intravenous [preservative free]:
Generic: 200 mcg/mL (100 mL, 200 mL); 10 mg/10 mL (10 mL [DSC]); 20 mg/20 mL (20 mL [DSC])
Stable in D5W, LR, 1/2NS, NS.
Y-site administration: Incompatible with furosemide, imipenem/cilastatin, procainamide.
Compatibility in syringe: Incompatible with furosemide.
Riociguat: Milrinone may enhance the hypotensive effect of Riociguat. Management: Riociguat is contraindicated with nonselective phosphodiesterase (PDE) inhibitors and PDE type 5 inhibitors. Other types of PDE inhibitors are not contraindicated, but caution is advised and patients should be monitored for hypotension. Monitor therapy
Platelet count, electrolytes (especially potassium and magnesium) and fluid status, renal function; ECG, blood pressure, heart rate; infusion site
If pulmonary artery catheter is in place, monitor cardiac index, stroke volume, systemic vascular resistance, pulmonary capillary wedge pressure and pulmonary vascular resistance.
Consult individual institutional policies and procedures.
>10%: Cardiovascular: Ventricular arrhythmia (ectopy 9%, NSVT 3%, sustained ventricular tachycardia 1%, ventricular fibrillation <1%)
1% to 10%:
Cardiovascular: Supraventricular arrhythmia (4%), hypotension (3%), angina/chest pain (1%)
Central nervous system: Headache (3%)
<1% (Limited to important or life-threatening): Anaphylaxis, atrial fibrillation, bronchospasm, hypokalemia, injection site reaction, liver function abnormalities, MI, rash, thrombocytopenia, torsade de pointes, tremor, ventricular fibrillation
Concerns related to adverse effects:
- Arrhythmias: Ventricular arrhythmias, including nonsustained ventricular tachycardia and supraventricular arrhythmias, have been reported. Observe closely for arrhythmias in this very high-risk patient population; sudden cardiac death has been observed. Due to the prolonged half-life as compared to other inotropic agents, ventricular or atrial arrhythmias may persist even after discontinuation of milrinone especially in patients with renal dysfunction (Cox 2013; Leier 1998). Ensure that ventricular rate is controlled in atrial fibrillation/flutter before initiating; may increase ventricular response rate. In heart transplant candidates, institute appropriate measures to protect patient against risks of sudden cardiac death (Brozena 2004).
- Hypotension: Hypotension may occur. Monitor blood pressure closely. Hypotension may be prolonged especially in patients with renal dysfunction (Cox 2013; Leier 1998). Vigorous diuresis may contribute to hypotension; cautious administration of fluids may be required to prevent hypotension. Omitting the bolus dose may decrease the risk of hypotension (Baruch 2001; Cuffe 2002). If hypotension occurs, consider dose reduction or temporary discontinuation.
Disease-related concerns:
- Cardiovascular disease: Avoid use in patients with severe obstructive aortic or pulmonic valvular disease in lieu of surgical relief of the obstruction; may aggravate outflow tract obstruction in hypertrophic cardiomyopathy with outflow tract obstruction.
- Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy to minimize the risk of arrhythmias.
- Renal impairment: Use with caution in patients with renal impairment; reduction in infusion rate recommended. Hypotension may be prolonged in patients with renal dysfunction (Cox 2013; Leier 1998).
Other warnings/precautions:
- Appropriate use: A facility for immediate treatment of potential cardiac events, including life-threatening ventricular arrhythmias, must be available. Safe and effective use beyond 48 hours (prolonged use) has not been demonstrated. An increased risk of death and hospitalization has been observed with prolonged use in NYHA Class III/IV heart failure patients. Sudden cardiac death has been reported with prolonged use. Continuous electrocardiographic monitoring is recommended.
- Long-term therapy: According to the ACCF/AHA 2013 heart failure guidelines, long-term use of intravenous inotropic therapy without a specific indication or for reasons other than palliation is potentially harmful (ACCF/AHA [Yancy 2013]).
C
Adverse events have not been observed in animal reproduction studies; however, increased resorption was reported in some studies.
A selective phosphodiesterase inhibitor in cardiac and vascular tissue, resulting in vasodilation and inotropic effects with little chronotropic activity.
Vd beta:
Infants (after cardiac surgery): 0.9 ‚ ± 0.4 L/kg (Ramamoorthy 1998)
Children (after cardiac surgery): 0.7 ‚ ± 0.2 L/kg (Ramamoorthy 1998)
Adults:
After cardiac surgery: 0.3 ‚ ± 0.1 L/kg (Ramamoorthy 1998)
Heart failure (with single injection): 0.38 L/kg
Heart failure (with infusion): 0.45 L/kg
Hepatic (minor); majority is not metabolized (Rocci 1987)
Urine (83% as unchanged drug; 12% as 0-glucuronide metabolite); active tubular secretion is a major elimination pathway for milrinone (Rocci 1987)
Clearance:
Infants (after cardiac surgery): 3.8 ‚ ± 1 mL/kg/minute (Ramamoorthy 1998)
Children (after cardiac surgery): 5.9 ‚ ± 2 mL/kg/minute (Ramamoorthy 1998)
Children (with septic shock): 10.6 ‚ ± 5.3 mL/kg/minute (Lindsay 1998)
Adults:
After cardiac surgery: 2 ‚ ± 0.7 mL/kg/minute (Ramamoorthy 1998)
Heart failure: 2.2 to 2.3 mL/kg/minute
IV: 5 to 15 minutes
Infants (after cardiac surgery): 3.15 ‚ ± 2 hours (Ramamoorthy 1998)
Children (after cardiac surgery): 1.86 ‚ ± 2 hours (Ramamoorthy 1998)
Adults:
Heart failure: 2.3 to 2.4 hours; renal impairment prolongs half-life (Rocci 1987)
Severe heart failure undergoing continuous venovenous hemofiltration (CVVH): 20.1 ‚ ± 3.3 hours (Taniguchi 2000)
Plasma: ~70%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache. Have patient report immediately to prescriber angina, tachycardia, severe dizziness, passing out, bruising, bleeding, or arrhythmia (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.